Berberine ameliorates NSAIDs-induced intestinal injury by the repair of enteric nervous system.
Fundam Clin Pharmacol. 2019 Sep 13. Epub 2019 Sep 13. PMID: 31520444
The study was to detect the role of GDNF, PGP9.5 (a neuronal marker) and GFAP (EGCs' marker) in the mechanism of NSAIDs related to intestinal injury, and to clarify the protective effect of berberine in the treatment of NSAID-induced small intestinal disease. 40 males SD rats were divided randomly into five groups (A-E): Group A: control group; Group B: model group received diclofenac sodium 7.5mg/(kg*d) for five days; Group C,D,E: berberine low, medium and high dose groups were treated by 7.5mg/(kg*d) diclofenac sodium for five days then received berberine 25mg/(kg*d) ,50mg/(kg*d), 75mg/(kg*d) respectively, between the sixth and eighth day. Intestinal mucosa was taken on the ninth day to observe the general, histological injuries, and to measure the intestinal epithelial thickness. Then, immunohistochemistry was performed to detect the expression of PGP9.5 and GFAP, and Western blot was performed to detect GDNF expression. The histological score and the general score in the model group were respectively 5.75±1.04 and 4.83±0.92. Scores in berberine medium and high berberine group were lower compared with the model group (P<0.05). The intestinal epithelial thickness in the model group was lower than in the control group and the berberine groups (P<0.05). PGP9.5, GFAP, GDNF content in the model group and the three berberine groups was significantly lower than in the control groups (P<0.05). PGP9.5, GFAP, GDNF content in the control group and the three berberine groups was higher compared with the model groups (P<0.05). Berberine can protect the intestinal mucosa of NSAID users and the mechanism is associated with the reparation of the ENS via up-regulating the expression of PGP9.5, GFAP and GDNF.